Research in human subjects will characterize the reinforcing effects of nicotine and caffeine and will investigate interactions between these drugs and cocaine. A series of six studies will focus nicotine, caffeine and cocaine administered intravenously to stimulant drug abusers in a residential research laboratory. Using choice procedures to assess relative reinforcing effects, one study will evaluate a range of nicotine doses and another study will evaluate a range of caffeine doses. Using similar procedures, a third study will directly compare the reinforcing effects of nicotine and cocaine, and a fourth study will compare nicotine and caffeine. Two other studies will examine the effects of acute caffeine pretreatment on the effects of intravenous nicotine and cocaine, and the effects of acute nicotine pretreatment on the effects of intravenous caffeine and cocaine. Concurrent with the residential studies, a series of five nonresidential studies will also focus on the reinforcing effects of and drug interactions between nicotine and caffeine in normal volunteers. Two studies will use drug discrimination procedures to determine whether familiarity with subtle mood-altering drug effects enhances the reinforcing effects of nicotine in nicotine non-users and oral caffeine in caffeine consumers. A third study will extend research on nicotine-caffeine interactions by determining whether chronic caffeine exposure enhances the reinforcing effects of nicotine in nicotine non-users. Another study will determine whether individual differences in the reinforcing effects of caffeine predict the reinforcing effects of nicotine in nicotine non-users. A final study will carefully characterize a group of caffeine dependent individuals, and evaluate the efficacy of a brief treatment intervention for caffeine dependence. This project will be of clinical importance in identifying determinants of vulnerability to nicotine and caffeine dependence in the general population. The studies with nicotine, caffeine and cocaine should also advance our understanding about drug interactions among these compounds and about pharmacological and behavioral mechanisms underlying stimulant drug abuse. Ultimately, this project should have relevance to the development of prevention and treatment strategies for stimulant drug abuse.